Medical Oncology Unit, University Hospital of Parma, Parma, Italy.
Radiology Unit, University Hospital of Parma, Parma, Italy.
Curr Drug Targets. 2018;19(14):1649-1656. doi: 10.2174/1389450119666180213102939.
Several reports attest the feasibility and the favorable outcomes of kinase inhibitors administration through feeding tubes or Percutaneous Endoscopic Gastrostomies (PEG), mainly in Non-Small Cell Lung Cancer (NSCLC) patients exposed to first-generation compounds. Here we present the case of an ALK-positive NSCLC patient who achieved cerebral and extra-cranial disease response with ceritinib (a novel ALK inhibitor) administered through a Nasogastric Tube (NGT). We moreover provide a review gathering clinical successes obtained with targeted agents intake through NGT or PEG.
A 53-year-old never-smoker woman was diagnosed with ALK-rearranged stage IV lung adenocarcinoma. After a brilliant response to crizotinib and several lines of systemic therapy, NGT positioning intended for ceritinib administration was required, given the development of a pleuro-esophageal fistula. Enteral drug administration allowed a significant reduction of hepatic and cerebral disease localizations.
The majority of kinase inhibitors administration through NGT or PEG accounts for EGFR-mutated (seven) or ALK-positive (seven, including our report) NSCLC patients. Five additional cases concerning different malignancies were described. Enteral drug administration was mostly required by disease-related respiratory impairment, requiring mechanical ventilation in the emergency setting. In our case, the cerebral and extra-cranial response obtained with enteral ceritinib intake suggests the proposition of novel inhibitors in these circumstances may take place after first-generation compounds failure or even upfront. Indeed, their grater potency and activity against brain metastases point out the role of their enteral administration in the first-line setting too, when a rapid systemic and intra-cerebral disease response is required.
有几项报告证实了通过饲管或经皮内镜胃造口术（PEG）给予激酶抑制剂的可行性和良好效果，主要是在接受第一代化合物治疗的非小细胞肺癌（NSCLC）患者中。在此，我们报告了一例 ALK 阳性 NSCLC 患者，该患者通过鼻胃管（NGT）给予塞瑞替尼（一种新型 ALK 抑制剂）后获得了脑内和颅外疾病缓解。此外，我们还回顾了通过 NGT 或 PEG 给予靶向药物治疗获得临床成功的病例。
一位 53 岁的从不吸烟女性被诊断为 ALK 重排的 IV 期肺腺癌。在对克唑替尼有显著反应并接受了几线系统治疗后，由于发生了食管胸膜瘘，需要进行 NGT 定位以给予塞瑞替尼。肠内药物给药显著减少了肝和脑内疾病的局部定位。
通过 NGT 或 PEG 给予大多数激酶抑制剂的情况涉及 EGFR 突变（7 例）或 ALK 阳性（7 例，包括我们的报告）的 NSCLC 患者。另外还描述了 5 例涉及不同恶性肿瘤的病例。肠内药物给药主要是由于与疾病相关的呼吸功能障碍引起的，在紧急情况下需要机械通气。在我们的病例中，通过肠内给予塞瑞替尼获得的脑内和颅外反应提示，在第一代化合物失败甚至初始治疗时，可能会考虑使用新型抑制剂。事实上，它们对脑转移的更强效力和活性表明，在需要快速全身和颅内疾病反应的情况下，它们的肠内给药也可能适用于一线治疗。
